Presently described is a case of disseminated adenovirus infection in a heart-kidney transplant recipient that was successfully treated with cidofovir. There are several reports of adenovirus infections in adult solid organ transplant recipients and the prognosis is usually poor, with mortality rates of 40% to 60%. Severe disseminated adenovirus infections have been associated with increased risk of adverse transplant events, such as rejection, ventricular dysfunction, allograft vasculopathy, graft loss, and the need for re-transplantation. The patients lack of clinical improvement, the onset of hemorrhagic cystitis and acute kidney injury were factors in our decision to temporarily discontinue administration of immunosuppressive agents and start an antiviral agent. It is important to suspect adenovirus in transplant patients when they do not respond to antibiotics and cultures are negative. Early diagnosis and treatment are critical to improving outcomes in immunocompromised patients.